Genetic Circuits in Salmonella typhimurium
Synthetic biology has rapidly progressed over the past decade and is now positioned to impact important problems in health and energy. In the clinical arena, the field has thus far focused primarily on the use of bacteria and bacteriophages to overexpress therapeutic gene products. The next generati...
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| Published in | ACS synthetic biology Vol. 1; no. 10; pp. 458 - 464 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Chemical Society
19.10.2012
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Synthetic biology has rapidly progressed over the past decade and is now positioned to impact important problems in health and energy. In the clinical arena, the field has thus far focused primarily on the use of bacteria and bacteriophages to overexpress therapeutic gene products. The next generation of multigene circuits will control the triggering, amplitude, and duration of therapeutic activity in vivo. This will require a host organism that is easy to genetically modify, leverages existing successful circuit designs, and has the potential for use in humans. Here, we show that gene circuits that were originally constructed and tested in Escherichia coli translate to Salmonella typhimurium, a therapeutically relevant microbe with attenuated strains that have exhibited safety in several human clinical trials. These strains are essentially nonvirulent, easy to genetically program, and specifically grow in tumor environments. Developing gene circuits on this platform could enhance our ability to bring sophisticated genetic programming to cancer therapy, setting the stage for a new generation of synthetic biology in clinically relevant microbes. |
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| AbstractList | Synthetic biology has rapidly progressed over the past decade and is now positioned to impact important problems in health and energy. In the clinical arena, the field has thus far focused primarily on the use of bacteria and bacteriophages to overexpress therapeutic gene products. The next generation of multigene circuits will control the triggering, amplitude, and duration of therapeutic activity in vivo. This will require a host organism that is easy to genetically modify, leverages existing successful circuit designs, and has the potential for use in humans. Here, we show that gene circuits that were originally constructed and tested in Escherichia coli translate to Salmonella typhimurium, a therapeutically relevant microbe with attenuated strains that have exhibited safety in several human clinical trials. These strains are essentially nonvirulent, easy to genetically program, and specifically grow in tumor environments. Developing gene circuits on this platform could enhance our ability to bring sophisticated genetic programming to cancer therapy, setting the stage for a new generation of synthetic biology in clinically relevant microbes. Synthetic biology has rapidly progressed over the past decade and is now positioned to impact important problems in health and energy. In the clinical arena, the field has thus far focused primarily on the use of bacteria and bacteriophages to overexpress therapeutic gene products. The next generation of multigene circuits will control the triggering, amplitude, and duration of therapeutic activity in vivo . This will require a host organism that is easy to genetically modify, leverages existing successful circuit designs, and has the potential for use in humans. Here, we show that gene circuits that were originally constructed and tested in Escherichia coli translate to Salmonella typhimurium , a therapeutically relevant microbe with attenuated strains that have exhibited safety in several human clinical trials. These strains are essentially nonvirulent, easy to genetically program, and specifically grow in tumor environments. Developing gene circuits on this platform could enhance our ability to bring sophisticated genetic programming to cancer therapy, setting the stage for a new generation of synthetic biology in clinically relevant microbes. |
| Author | Prindle, Arthur Hasty, Jeff Goldberg, Anna Selimkhanov, Jangir Danino, Tal Bhatia, Sangeeta N Samayoa, Phillip |
| AuthorAffiliation | Massachusetts Institute of Technology University of California, San Diego |
| AuthorAffiliation_xml | – name: Massachusetts Institute of Technology – name: University of California, San Diego |
| Author_xml | – sequence: 1 givenname: Arthur surname: Prindle fullname: Prindle, Arthur – sequence: 2 givenname: Jangir surname: Selimkhanov fullname: Selimkhanov, Jangir – sequence: 3 givenname: Tal surname: Danino fullname: Danino, Tal – sequence: 4 givenname: Phillip surname: Samayoa fullname: Samayoa, Phillip – sequence: 5 givenname: Anna surname: Goldberg fullname: Goldberg, Anna – sequence: 6 givenname: Sangeeta N surname: Bhatia fullname: Bhatia, Sangeeta N – sequence: 7 givenname: Jeff surname: Hasty fullname: Hasty, Jeff email: hasty@ucsd.edu |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23097749$$D View this record in MEDLINE/PubMed |
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| Issue | 10 |
| Keywords | S. typhimurium genetic circuits microfluidics clinical synthetic biology |
| Language | English |
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| Snippet | Synthetic biology has rapidly progressed over the past decade and is now positioned to impact important problems in health and energy. In the clinical arena,... Synthetic biology has rapidly progressed over the past decade and is now positioned to impact important problems in health and energy. In the clinical arena,... |
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| Title | Genetic Circuits in Salmonella typhimurium |
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